Preparation of heterocyclic compounds



Patented July 15, 1952 s PATENT OFFICE I PREPARATION OF HETEROCYCLIC V COMPOUNDS Louis Schmcrling, Riverside, 111., assignor to Universal Oil Products Company, Chicago, 111.; a

corporation of Delaware No Drawing; Application July 25, 1947,, a I Serial No. 763,735 I l 16 Claims. (01. 260327) This application is a continuation-in part of my copending application SerialNo. 741,945'fi1ed April 16, 1947, now abandoned. e c I'hisinvention-relates to a process for preparing-a particular typeof 'heterocyclic compounds containing-a non-metal of group VI of the periodic table and, particularly, tothe preparation of heterocyclic compounds containing oxygen and sulfur. a An object o'f' this invention is the production of. 'aFheterocyclic compound containing-a nonmetal :of group VI of theperiodic table and in which one of the carbon atoms of the heterocyclic ring is a quaternary carbon atomp Another object of this invention is the production of a heterocyclic compoundcontaining oxygenand in whichonexofthe carbon atoms of the heterocyclic ring is a quaternary carbon atom.

Still another object of a this inventionv is the production of a heterocyclic compoundcontaining sulfur and in which one of the carbon atoms of-ethe heterocyclic ring is-aquaternary carbon atomnyui 3 A further object of this invention is the produc tion of a 4,4-dialkyltetrahydropyran; V

.,A,stil1 further object of this invention isthe production, of a, 4,4-dialkyltetrahydrothiopyran.

Onespecific embodiment of; this invention relates to, a process for preparingv a heterocyclic compound containing a quaternary carbon atom which; comprises reactingv an olefin and a .saturated ,idihalogenated' hydrocarbon which represented by the formula:

" R oH,-; c-1'(o11, -R-,

imwhich R, R, R", and R" each" represents a memberof the groupconsisting of hydrogen, an alkyleradical, and a'cycloalkyl' radical, X represents'a halogen, and n'is a character of the group consisting of v0, 1,; and 2, in the'presence'of a Friedel-Crafts catalyst to iorm'a'dihalogenated saturated hydrocarbonrontaining a quaternary carbon atom, recovering theidihalogenated saturated hydrocarbon fromv the reaction mixture, reacting said dihalogenated saturated hydrocarbonwith a binary compound of a metal selected from the members of the group consisting. of the alkali and alkaline earth metalstand a non-metal of group VI of the periodic table to form a heterocyclic compound containing said non-metal and havinga quaternary, carbon atom, and recovering saidheterocyclicfc'ompound;

Another embodiment of this invention relatesito III I may be a process for preparing a heterocyclic compound containing a quaternary carbon atom which comprises reacting a mono-olefin and a'saturated dichloroalkane which may be represented by the formula: M

V 01 c1 RCH:J3(CHz)-,R

R! H: II! in which R, R, R and;R"' each represents a member of the group consisting of hydrogen, an alkyl radical, and a cycloalkyl radical, and n is a character of the group consisting of 0, 1, and 2 in the presence of a FriedeleCrafts catalyst to form a dichloroalkane containing a iquaternary carbon atom, recovering the last-named dichloroalkane and reacting .it witha binary compound of an alkali metal and of a non-metal of group VI of, the periodic table to formeaheterocyclic compound containing said non-metal and having a quaternary carbon atom, and: recovering said heterocycliccompound. V

Accordingto this process, aheterocyclic compound containing a 'quaternary carbon atom is prepared by condensing a mono-olefin and a di-, haloalkane, which maybe representedbyi the formula: y

R-oir,-bori,),,-t'-R" SB' i in, which R, R, R", and R eachrepresents a member of the group consistingof hydrogen, an alkylradical, and a cycloalkyl radical-QX represents a-,halogen fipreferablya middle halogen, thatis, chlorine or bromine), and niis a character of the groupconsistingoffl, -1,an,d 12, to,form a higher molecular weight dihaloalkane containing a quaternary carboniatom, and said vdihaloalkane is then heated; ;with a n oxide; sulfide, se1enide,. or telluride of a 7 metal ;andjpreferably of an alkali'n etaloralkaline earth metal, and usually in the presenceof fwater, to produce the desired heterocyclic compound, These oxides, sulfides, selenides, and tellurides are binary compounds of metals and non-metals of group VI of the periodic table.

In the first step or thisprocess', saturated d1 halogenated hydrocarbons are formed by "reacting anolefin with a saturated'dihalogenated hydrocarbonpthatjis, a dihaloalkane or dihalocycloalkane, in which at least one of .thehalogen atoms is attached to a tertiary carbon atorrr; The preferred halogens are chlorinefand' bromine whichare sometimes referred to-as-" the-middle halogens. These dihalogenated hydrocarbon starting materials for this process may be represented by the following formula:

in .which R R; R" and R' each represents a 'memberof the group consisting'of hydrogen, an

alkylradical, and a cycloalkyl radical, X represents a halogen (preferably chlorine or bromine), and n is a character of the group consisting of 0,

l, and 2. Also in some modifications of'this invention, two of the R groups maybe combined-to form a cycloalkane ring. 7

The 7 character n shown in .7 the. preceding 1 formulae and also shown hereinafter in the equations illustrating the type of heterocyclic compounds formed by this'process has a value seinvention range fromjsuch active catalysts as aluminum chloride and aluminum bromide to catalysts of intermediate activities as ferric chloride and boron fluoride and such catalysts of mild activities as bismuth chloride, zinc chloride, titaniumtetrachloride and the like. Mo-

' lecularcomplexesof these FriedelrCrafts halide catalysts with oxygen-containing compounds such as the alcoholates, etherates, ketonates, and complexes with nitroparafiins may' also be used. Thegcatalystsludges formed in this process contain a Friedel-Crafts catalyst and may also be recycled and utilized for condensing dihaloalkanes andj olefi-nic hydrocarbons as herein set forth when employing Friedel-Crafts catalysts. The reaction temperature used in the process will depend 'upon. the particular reactants and also upon the catalyst employed. While the processiis generally carried out at a temperature minum chloride, aluminum bromide, ferric V of from about-C.]to about 100 C;, a tem-: perature of v fromjabout --4Q to about c+5 0- C. is preferred when using catalystscomprisingalu chloride, o and boron fluoride while temperatures of'from: about 0 to about 10080.; are :used r-w-ith most of the'other metal halide catalysts such. as;

group; and when the symbol V(CH2)n;

represents the group b v dihalogenated saturated'fhydrocarbon and olefin are combined inthelpr'e'sence ofa Friedel- Crafts catalyst, including'boron fluoride, to-form a higher .boiling dihalogenated hydrocarbon with a molecular weight equal to the sum of themelecular'weightsof thereactants;- The best yields.

ofcondensation products are u'suallyobtained when using as starting material a dihalogenated saturated hydrocarbonin which the halogens are combined' with one-tertiary and onenontertiary carbon .atomJ"Thesedihalog'enated saturated hydrocarbons include isoprene 'dihy-' drochloride- (more exactly referred to as 1,3- dichloro-3-methylbutane), isoprene dihyd-robromide, 1,2-dichloro-Z-methylpropane and 2-methylpentadiene dihydrochloride (also referred to as 2,4-dichloro-2-methylpentane).' Typical saturated dihalogenated hydrocarbons in which both halogen atoms are attached to tertiary carbon] 7 atoms are. 25 edichlbro -2,5i-'dimethylliexane, lim-H onenez dihydroch-loride (that is, '1-.chloro- 4-( 1- chloroeisop'ropyl) -l-me'thylcyclohexane) and'2g3- dibromo-Z,3 -di-methylbutane. Someofthesedihalides are crystalline compounds which are pref- 1 erablywdissolved in'an' inert solvent such as pentane before being 'subjected to the condensa-r tion-reactionwithan olefin. y I

Olefinic hydrocarbonsutiliza le inthisprocess' include ethylene, propylene, the butylenes; the;

" pentenes; hexenes; and higher boiling normally liquid alkenes aswell as various cyclic olefinsj including-- cyclopentene and cyclohexene hydrocarbons; Ethylene is the olefinpreferred m1 condensation with dihalogenated hydrocarbons as the resultant higher molecular weight polyhaloi saturated hydrocarbon contains at least one primary halogfi l atom, that, the halogen, is bound to a carbonatom'atthe end ofthe carbon chain, said carbon atom beingfalso combined with two r g atom l I Catalys s. sui 172 3? inflthwe; pro ess- OET hi-SV V bismuth chloride,rzinc chloride, titanium chloride.

This process may be carried out using eitherbatch or continuous typesoiioperation, InIbatchtype: treatment the dihalogenated saturated hydrocarbon and an olefin are-reacted inthe pres: V

'ence of .one or more of; the; above indicated: halide catalystsin a closedreactopprottided. with ade-x quate means of agitation and maintained at a V temperature at which theecondensation "reaction is effected, The resultant-., reaction; mixture. is.

' c then subjected to suitable septmratingitreatment:

to recover unconverted reactants which rare. suitable iorfurthertreatment in the process. and to, V I isolate th'e.v desired dihalogenated condensation product which' is, then reacted; with an oxide, sulfide, selenide, or telluride of a metal and preferably of an alkali metal 'oi alkaline earthimetal to form a heterocyclic compounds charging .the ol'efinic compound and dihalogene ated: saturated hydrocarbon to a reactor-containing a; Friedel-Crafts metah alidecatalyst; par-'- ticularly, aluminumchloride; distributed "uponor composited with a supporting material such as silica; alumina, charcoali or -another carrier andzprovided with suitableheatiiig orboolih'g means for controlling the reaction temperature.

When operating with a catalystwhich is soluble in the reaction mixture atj the'lreaction conditions, the catalyst may be' charged continuously f othe. reactor.- to which ;,the dihalogenatedisatu rated 7 hydrocarbon. ;a:nd1,.olefi n; are echargedziiOn-x the catalyst may be dissolved in ,a. .suitab l solvent; 7 such, as. anitroparaflin andzachargedsicohtinuousei 13! together with the mixture of, reactants-313 mm;

the exit end of .the. reactornriseriesE 'oftreactora: in. case more than one reactorzis" used; the reactionmixture isdirected'; to.- suitableilseparatingv and/or fractional distilling Imeans by; which the dihalogenated saturated. hydrocarboniformed-P in the process may be separated from ilthaunco'na verted starting material 'iahdilcatalystgthese lun converted materials and e'c'a'talysi; ibei'ng: suitable-'- for recycling tothe process; V l V Condensation of ethyleneiandia saturateddia.

halogenated hydrocarbon i-inf:which one of the halogen atomszisJcombin'ed with 'altertiary car-- bon; atomjinjtheapresjence: oi zaliimiiiumichloride Continuous operation;maybe-carried out by l gives an excellent yiem, or a dihalogenated satu:

rated hydrocarbon containing a quaternary carbon atom and in which at least one. oi the haloen atoms-. sa tached e prim y carbo a Dihalogenated saturated hydrocarbons of the type'; formed as herein set 'forthtare useful" intermediat'es for organic syntheses since they offer a"c onvenient"means for preparing many compounds including heterocyclic compounds. For

example, -1,5-dihalo-3,3-dimethylpentane' which is formed by. condensing ethylene with isoprene dihydrohalide is a suitable intermediate for preparing-heterocyclic' compounds. containing six atoms in a ,ifi'ng' five of which are carbon atoms. For example; "1.5;dichloro-3,3-dimethylpentane reacts .with ,water and alkali or alkaline earth metal oiiides, sulfides, selenides, and tellurides to form 4,4-dimethyltetrahydropyran, 4,4-dimethyltetrahydrothiopyran, 4,4 dimethyltetrahydroselenopyran, and 4,4-dimethyltetrahydrotelluropyran, respectively.

The reactions which may thus be employed in producing heterocyclic compounds by this process may be represented by the following equations:

In these equations, R and R are selected from the group consisting of hydrogen and alkyl and cycloalkyl radicals, X is a halogen (preferably chlorine or bromine) and n is a character or the roup c si tin .qfi0.. Land 2.:, such. hetero-I;

be represented by. the

cy licr mpo d may formula:

- f .n'omnion i yh ch 15. a?

' iiThe f examples are given to illustrate the-process of this invention although the data arc. Enot introducedwith. the. intention of limit v ing unduly the broad scope of the invention.

Example I 1,5-dichloro-3,3-dimethylpentane was prepared in about of the theoretical'yield by the condensation of ethylene with isoprene dihydrochloride (i. e., 1,3-dichloro-3-methylbutane) in the present of aluminum chloride at -20 to -'-l0 C. When the resultant dichlorodimethylpentane was heated at 250 0. with a molecular excess of magnesium oxide suspended in ten times its weight of water, there was obtained an excellent yield of a new compound, 4,4-dimethyltetrahydropyran, B. P., 124 to 126 C., 11 1.4238.

Example II When the dichlorodimethylpentane, prepared as described in Example I, was heated with an aqueous solution of sodium sulfide at 210 C., 4,4-dimethyltetrahydrothiopyran was obtained in excellent yield. It boiled at 58 C. at 13 mm. pressure (about 168 C. at atmospheric pressure) and had a refractive index n of 1.4900.

I claim as my invention:

1. A process forz'producing a heterocyclic compound containing a quaternary carbon atom which comprises reacting a 1,5-dihalo-3,3-di-- alkylpentane with a binary compound of a metal and of a non-metal of group VI of the periodic table at a temperature of from about C. to about 300 C. and in the presence of a suspending medium for said binary compound consisting essentially of water.

2. The process of claim 1 further characterized in that said metal is an alkali metal.

3. The process of claim 1 further characterized in that said metal is an alkaline earth metal.

4. The process of claim 1 further characterof an alkali-metal. I 12. A process for producing 4,4-dimethyltetrahydropyran which comprises heating 'LS-dichime-3,3-dimethylpentai1e with a5. metal oxide at. a; temperature; ofzfronr ahout 150% 03120 about 300?": i042 and; in itlie;.;presence.of.:ia suspending V i egtoegeat ized ir-i that said binarycompoundis -an oxide of: a metal selected from the group consistingbf the alkali and alkaline earth metals.

'5. The process of claiml further characterized in that said binary compound is a sulfide of a metal selected from the group co'nsisting of the alkali and alkaline earth metals.

6. A process for producing a heterocyclic compound containing a quaternary carbon atom which comprises reacting-1,5-dich1oroa3,3 -dimethylpentane with a; binary compound; ot a metal; and of a ncn-metar or group VI '{of the periodic table am -tempgmure of "from; about 150 Qfto ab iIt BOO 'Q- and-in the presence' -of a suspending -mediumfdr s'aid binary com-pound co'nsistirigfessentially of'water 1 l g "Zlhe' processor-clam fi' iurthercharacterized in thafisaid l metal is an alkali metal;

8, The process of claim 6 further characterized in thatsaid metal is an alkaline earth metal-.-

9. The" process of claim 6 further characterized in'that said binary compound is an oxide ,of a metal selected from the group consisting of the alkali and alkaline earth metals.

10. The process of claim 6 further characterized in that said binary compound is r a sulfide of a metal selected from the group consisting of the alkali and alkaline earth 'metals. V

11. The processof claim 6 further characterized in that. said binary compound is aselenide medium" f0" said oxide fconsls'ti-rig e'ssentiaflly of '13 ."-'I 'I-1e 15r6e- SS Q1 aini-izjfurthercharactev izedin' thatsaid-ox ide=isjnag=nesiumjoxida 14. A process for: producing4dimethyltetra hydrothiopyran which comprises heating 1,5-dir chloro-3,3-dimethylpentane with a; metal sulfide at a temperature of 'fi'oni'about "160 CJto about 300 C. and in the'presence of-' a suspending medium for said sulfide consisting essentially of' water. c

15. The process of claim 14 further characterized in that said sulfide is an alkali metal sulfide.

16. 4,4-dimethyltetrahydrothiopyran.V

' LOUISi SCHMERLING. "REFERENCES oimED' The following references file of this patent; j V

UNITED STATES PATENTS a E THERR F RENCES- an mi mae mdts; sari-111' out.

are of record in the 

1. A PROCESS FOR PRODUCING A HETEROCYCLIC COMPOUND CONTAINING A QUATERNARY CARBON ATOM WHICH COMPRISES REACTING A 1,5-DIHALO-3,3-DIALKYLPENTANE WITH A BINARY COMPOUND OF A METAL AND OF A NON-METAL OF GROUP VI OF THE PERIODIC TABLE AT A TEMPERATURE OF FROM ABOUT 150* C. TO ABOUT 300* C. AND IN THE PRESENCE OF A SUSPENDING MEDIUM FOR SAID BINARY COMPOUND CONSISTING ESSENTIALLY OF WATER. 